Injectable Silk-Based Hydrogel as an Alternative to Cervical Cerclage: A Rabbit Study

• Published in: Tissue engineering. Part A 2020-04, Vol.26 (7-8), p.379-386
• Main Authors: Zhang, Yali, Raia, Nicole, Peterson, Ashley, Kaplan, David L, House, Michael
• Format: Article
• Language: English
• Subjects: Animal models; Biocompatibility; Biodegradation; Birth; Cervix; Compression; Hydrogels; Infants; Inflammation; Injection; Mechanical properties; Morbidity; Original; Original Articles; Polyethylene; Polyethylene terephthalate; Pregnancy; Premature birth; Silk; Sutures
• ISSN: 1937-3341; 1937-335X
• DOI: 10.1089/ten.tea.2019.0210

Background: Preterm birth is a common cause of morbidity and mortality in newborn infants. Cervical insufficiency (CI) is a significant cause of preterm birth. The treatment for CI is cerclage, which is a suture placed around the cervix to provide mechanical support. Cerclage, however, is associated with limited efficacy. Here we present an injectable, silk-based hydrogel as an alternative to cerclage. Objective: Pregnant rabbits were used as an animal model of pregnancy to study the mechanical properties, biocompatibility, and degradation of the hydrogel after cervical injection. Study Design: Silk hydrogel (200 μL volume) was injected into the cervix. Controls were either injected with saline or treated with cerclage (5-0 polyethylene terephthalate suture). To study the effect on mechanical properties, the cervix was tested in compression. Biodegradation of the hydrogel was followed over 6 weeks. For biocompatibility, expression levels of proinflammatory mediators were studied. Results: Hydrogel injection resulted in significant tissue augmentation—the cross-sectional area of the cervix increased 46.3 ± 3.0%. The modulus of the uninjected and hydrogel-injected tissues was 3.3 ± 0.7 and 3.2 ± 0.5 kPa at 5–10% strain, respectively ( p  = 0.8). Histology showed a mild inflammatory response surrounding the hydrogel. Biodegradation of the hydrogel showed 70% volume loss over 6 weeks. Hydrogel-injected tissue showed similar inflammatory response compared with cerclage. Conclusions: In pregnant rabbits, cervical injection of the silk-based hydrogel was biocompatible and naturally degraded. No adverse effects on timing of delivery and pup viability were seen. Silk-based hydrogels show promise for tissue augmentation during pregnancy.